Post Flu Shot Confusion – think ADEM!

a Residents in the Department of Internal Medicine at Texas Tech University Health Sciences Center in Amarillo, TX. Akram Zaqooq is an assistant professor in the Division of Critical Care Medicine at TTUHSC in Amarillo, TX.

Abstract

A 57-year-old Caucasian man with hypertension and diabetes presented with left
arm weakness and headache for one day. He had an influenza vaccination 10 days prior
to presentation. Computed tomography (CT) of the head showed a possible right MCA
stroke. The next day he developed left hemiplegia. A repeat CT of the head exhibited
a “mass like” effect in the right hemisphere. Magnetic resonance imaging (MRI) of the
head showed a diffuse area of abnormal signals, involving both hemispheres, and diffuse
white matter changes. His CSF showed WBC 4/mm3, RBC 1/mm3, glucose 97 mg/dl, and
protein 96 mg/dl. He continued to deteriorate, developed encephalopathy, and had to be
intubated. A repeat MRI of the head demonstrated extensive bilateral, poorly marginated
white matter, and some grey matter involvement characteristic of acute disseminated
encephalomyelitis (ADEM). He failed to respond to methylprednisolone 1 gram daily and
was started on plasma exchange daily for 10 days. He started to improve after the second
session. After five months he was essentially normal and had returned to work. This
case demonstrates that routine vaccination can have important complications.

Introduction

Vaccines have a major role in preventing disease
but do have side effects. Although most serious
adverse effects are rare following vaccination,
it is important to recognize them, as they could be
potentially life threatening. Acute disseminated encephalomyelitis (ADEM), a demyelinating disease of
the nervous system, is one such complication. Fewer
than 5% of ADEM cases are associated with vaccinations.
There is little knowledge about its pathogenesis,
and treatment options are based on small case series. Here we report a 57-year-old Caucasian man who developed ADEM 10 days following an influenza vaccination. The goal of this report is to alert health care providers about such rare occurrences.

Case

We report a 57-year-old Caucasian man
with hypertension and type 2 diabetes. He was an
ex-smoker but denied any history of alcohol or substance
abuse and any family history of neurological
disorders. He was well until one day prior to admission,
when he presented with left arm weakness,
slurred speech, and headache. Clinical examination
and computed tomography (CT) of the head suggested
acute right middle cerebral artery ischemic stroke, and he was admitted to a stroke unit for management.
However, over the next 24 hours, he developed an
altered mental status with worsening weakness in his
left arm and new weakness in his left leg. On further
inquiry, his family reported that the patient had received
an influenza vaccination 10 days prior to his
presentation.
Neurological examination on the day of admission
revealed a Glasgow Coma Scale (GCS) of
15 and left arm power of 2/5. The rest of his examination
was essentially normal. Laboratory results were
within normal limits except for HbA1c of 13%. On
day two, his GCS deteriorated to 12 (E4, V3, M5).
Vital signs remained normal with BP 132/78 mmHg,
temperature 97.2 °F, respiratory rate 16 breaths per
minute, and heart rate 84 beats per minute. His CBC
and chemistry panel were unchanged from day one.
A repeat CT of the head showed possible mass effect
in the right frontal hemisphere. Magnetic resonance
imaging (MRI) of the head showed a diffuse
area of abnormal signals involving both hemispheres
and diffuse white matter changes. The differential diagnoses
included infection, infiltrating neoplasm, and
demyelinating diseases. He was started on acyclovir, ceftriaxone, and vancomycin for possible meningoencephalitis.
On day three, his neurological status deteriorated.
He developed spasticity in his arms and legs
and had an altered mental status to a point that he
needed intubation for airway protection. Opening
pressure, on lumbar puncture, was normal, and CSF
analysis showed a WBC count 4/mm3 (lymphocytes
only), RBC 1/mm3, glucose 97 mg/dl, and total protein
96 mg/dl. Over the next 24 to 48 hours, the patient
did not improve. A repeat MRI (Figure 1, 2) showed
bilateral, poorly marginated, multifocal and extensive
white matter, and some gray matter lesions of the
same age. These findings suggested acute disseminated
encephalomyelitis. Methylprednisolone, 1 gm
daily, was started. An extensive workup was done to
rule out other diagnoses, such as HIV leading to PML,
multiple sclerosis, vasculitis, Lyme disease, other viral
and fungal encephalitis, and prion diseases (mainly
CJD); all results were negative (Table). The CFS
analysis showed increased IgG and IgG synthesis
and a positive myelin basic protein, which implied an
immunological process.

Figure1: T2 FLAIR Image. Extensive hyperintense signals on T2 FLAIR involving deep white matter of the both frontal and parietal lobes bilaterally. It exhibits multifocal, bilateral, poorly marginated white matter disease. It also shows gray matter involvement, where the cortex is very thin (red arrows in Figure 2). All lesions are about the same age. There is minimal midline shift.

Discussion

Acute disseminated encephalomyelitis is an
autoimmune demyelinating disease of the nervous
system, commonly triggered by infection or immunization.
Fewer than 5% of ADEM cases are preceded
by vaccination1, and the usual onset is within 1 month
post-vaccination.2 The typical presentation includes
acute onset of encephalopathy (75%), multifocal neurological
ﬁndings, rapid deterioration, and a monophasic
illness.3 In our case, the patient received influenza
vaccine 10 days prior to presentation. If treatment is
provided in a timely manner, full recovery occurs in 50
to 75 % of patients within 1 to 6 months.2

Diagnosis

The CSF analysis confirmed that patient had
an immunological insult. The CSF results, the characteristic
MRI, and clinical findings confirmed our suspicion
of ADEM. He met level 1 diagnostic certainty
criteria for ADEM according to Brighton Collaboration
Encephalitis Working Group.4He demonstrated
multifocal neurological findings, characteristic MRI
findings, and his illness was monophasic. He developed encephalopathy, which is present in up to 75
% of patients with ADEM.5 He had left visual neglect,
left upper motor facial weakness, left hemiplegia, and
increased spasticity in lower extremities. His MRI
showed characteristic findings for ADEM with multifocal,
bilateral, poorly marginated white matter disease
with hyperintensities on T2 FLAIR image.1 It also
showed gray matter involvement (red arrows in figure
2) which helps differentiate ADEM from multiple
sclerosis (MS), since MS does not have gray matter
involvement. All lesions of about the same age are
another typical finding of ADEM on MRI, unlike MS in
which older lesions appear as black holes. The third
important feature of ADEM is the monophasic illness,
i.e., patients should not have relapse of disease for at
least for 90 days after a symptomatic nadir. Our patient
was followed for five months and had no relapse
of any symptoms. To prove whether ADEM in this patient
was caused by the influenza vaccine or whether
it was a temporal coincidence is difficult, as there is
no definitive test available to prove this. According to
the World Health Organization causality assessment
criteria6, it was very likely that ADEM was caused by
the influenza vaccine that the patient received 10
days prior to presentation.

Management

Most treatment options for ADEM are based
on case reports or on small clinical series. There are
no randomized clinical trials to identify a preferred
treatment. Three main treatments have shown benefit:
high dose corticosteroids, plasma exchange therapy,
and IV immunoglobulins.1,2 The first line therapy
is high dose corticosteroids. The most commonly
used regimen is methylprednisolone 1 gm IV daily for
3 to 5 days followed by 28 days of tapering prednisone.
If treatment with corticosteroids does not produce
improvement, the second line therapy is plasma
exchange.1 Most literature recommends 5 to 10 sessions
of plasma exchange. Intravenous immunoglobulin
is used only if plasma exchange is not available
or contraindicated. In our case, the patient did not
show any improvement after 1 gm methylprednisolone
IV for three days and was started on plasma exchange
therapy. He received one session daily for 10
days and started improving after the second session.
Within five months he had returned to work without
any difficulties.

A 54-year-old obese woman with a history of cardioverter defibrillator implantation (ICD) in 2004 for symptomatic ventricular tachycardia presented with discomfort at the site of the pulse generator and a “feeling of a knot”.